title: Antiplatelet activity of Phellinus baummii methanol extract is mediated by cyclic AMP elevation and inhibition of collagen-activated integrin-α(IIb) β₃ and MAP kinase.
abstract: Phellinus baumii is a mushroom that has been used as folk medicine against various diseases and is reported to have antidiabetic, anticancer, antioxidant, antiinflammatory and antihypertensive activities. However, information on the effects of P. baumii extract in platelet function is limited. Therefore, the aim of this study was to examine the impact of a P. baumii methanol extract (PBME) on platelet activation and to investigate the mechanism behind its antiplatelet activity. PBME effects on agonist-induced platelet aggregation, granule secretion, [Ca²⁺](i) mobilization, α(IIb) β₃ activation, cyclic AMP release and mitogen-activated protein kinase (MAPK) phosphorylations were studied using rat platelets. PBME dose-dependently inhibited collagen, thrombin and ADP-induced platelet aggregation with an IC₅₀ of 51.0 ± 2.4, 54.0 ± 2.1 and 53.0 ± 4.3 μg/mL, respectively. Likewise, thrombin-induced [Ca²⁺](i) and collagen-activated ATP secretions were suppressed in PBME treated platelets. Aggregation and ATP secretion were also markedly attenuated by PBME alone or in combination with PP2 (Src inhibitor) and U-73122 (PLC inhibitor) in collagen-stimulated platelets. Besides, PBME treatment elevated basal cyclic AMP levels and inhibited collagen-induced integrin-α(IIb) β₃ activation. Moreover, PBME attenuated extracellular-signal-regulated protein kinase 2 (ERK2) and c-Jun N-terminal kinase 1 (JNK1) phosphorylations. Further PD98059 (ERK inhibitor) and SP60025 (JNK inhibitor) reduced collagen-induced platelet aggregation and ATP secretion. In conclusion, the observed PBME antiplatelet activity may be mediated by activation of cyclic AMP and inhibition of ERK2 and JNK1 phosphorylations. Finally, these data suggest that PBME may have therapeutic potential for the treatment of cardiovascular diseases that involve aberrant platelet function.
authors.affiliation: College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: S M
authors.initials: SM
authors.lastname: Kamruzzaman
authors.forename: Mehari
authors.initials: M
authors.lastname: Endale
authors.forename: Won-Jun
authors.initials: WJ
authors.lastname: Oh
authors.forename: Seung-Chun
authors.initials: SC
authors.lastname: Park
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Kim
authors.forename: In-Kyoung
authors.initials: IK
authors.lastname: Lee
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
authors.forename: Hwa-Jin
authors.initials: HJ
authors.lastname: Park
authors.forename: Sang Keun
authors.initials: SK
authors.lastname: Kim
authors.forename: Bong-Sik
authors.initials: BS
authors.lastname: Yun
authors.forename: Man Hee
authors.initials: MH
authors.lastname: Rhee
mesh_terms: D000363:Agaricales / Q000737:chemistry; D000818:Animals; D001487:Basidiomycota / Q000737:chemistry*; D001688:Biological Products / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D003094:Collagen / Q000037:antagonists & inhibitors; D000242:Cyclic AMP / Q000378:metabolism*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013917:Thrombin / Q000037:antagonists & inhibitors
chemical_list: D001688:Biological Products; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D003094:Collagen; D000242:Cyclic AMP; D019950:Mitogen-Activated Protein Kinase 1; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D013917:Thrombin